In vivo dynamics of acidosis and oxidative stress in the acute phase of an ischemic stroke in a rodent model

Ischemic cerebral stroke is one of the leading causes of death and disability in humans. However, molecular processes underlying the development of this pathology remain poorly understood. There are major gaps in our understanding of metabolic changes that occur in the brain tissue during the early...

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Autores principales:	Ilya V. Kelmanson, Arina G. Shokhina, Daria A. Kotova, Matvei S. Pochechuev, Alexandra D. Ivanova, Alexander I. Kostyuk, Anastasiya S. Panova, Anastasia A. Borodinova, Maxim A. Solotenkov, Evgeny A. Stepanov, Roman I. Raevskii, Aleksandr A. Moshchenko, Valeriy V. Pak, Yulia G. Ermakova, Gijsbert J.C. van Belle, Viktor Tarabykin, Pavel M. Balaban, Ilya V. Fedotov, Andrei B. Fedotov, Marcus Conrad, Ivan Bogeski, Dörthe M. Katschinski, Thorsten R. Doeppner, Mathias Bähr, Aleksei M. Zheltikov, Dmitry S. Bilan, Vsevolod V. Belousov
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Ischemic stroke Ischemia/reperfusion Hypoxia/reoxygenation In vivo optical brain interrogation Genetically encoded fluorescent biosensors Hydrogen peroxide Medicine (General) R5-920 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/1a45f757a0164abd98bbabfc20e1314f
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spelling	oai:doaj.org-article:1a45f757a0164abd98bbabfc20e1314f2021-11-12T04:33:07ZIn vivo dynamics of acidosis and oxidative stress in the acute phase of an ischemic stroke in a rodent model2213-231710.1016/j.redox.2021.102178https://doaj.org/article/1a45f757a0164abd98bbabfc20e1314f2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2213231721003384https://doaj.org/toc/2213-2317Ischemic cerebral stroke is one of the leading causes of death and disability in humans. However, molecular processes underlying the development of this pathology remain poorly understood. There are major gaps in our understanding of metabolic changes that occur in the brain tissue during the early stages of ischemia and reperfusion. In particular, it is generally accepted that both ischemia (I) and reperfusion (R) generate reactive oxygen species (ROS) that cause oxidative stress which is one of the main drivers of the pathology, although ROS generation during I/R was never demonstrated in vivo due to the lack of suitable methods. In the present study, we record for the first time the dynamics of intracellular pH and H2O2 during I/R in cultured neurons and during experimental stroke in rats using the latest generation of genetically encoded biosensors SypHer3s and HyPer7. We detect a buildup of powerful acidosis in the brain tissue that overlaps with the ischemic core from the first seconds of pathogenesis. At the same time, no significant H2O2 generation was found in the acute phase of ischemia/reperfusion. HyPer7 oxidation in the brain was detected only 24 h later. Comparison of in vivo experiments with studies on cultured neurons under I/R demonstrates that the dynamics of metabolic processes in these models significantly differ, suggesting that a cell culture is a poor predictor of metabolic events in vivo.Ilya V. KelmansonArina G. ShokhinaDaria A. KotovaMatvei S. PochechuevAlexandra D. IvanovaAlexander I. KostyukAnastasiya S. PanovaAnastasia A. BorodinovaMaxim A. SolotenkovEvgeny A. StepanovRoman I. RaevskiiAleksandr A. MoshchenkoValeriy V. PakYulia G. ErmakovaGijsbert J.C. van BelleViktor TarabykinPavel M. BalabanIlya V. FedotovAndrei B. FedotovMarcus ConradIvan BogeskiDörthe M. KatschinskiThorsten R. DoeppnerMathias BährAleksei M. ZheltikovDmitry S. BilanVsevolod V. BelousovElsevierarticleIschemic strokeIschemia/reperfusionHypoxia/reoxygenationIn vivo optical brain interrogationGenetically encoded fluorescent biosensorsHydrogen peroxideMedicine (General)R5-920Biology (General)QH301-705.5ENRedox Biology, Vol 48, Iss , Pp 102178- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Ischemic stroke Ischemia/reperfusion Hypoxia/reoxygenation In vivo optical brain interrogation Genetically encoded fluorescent biosensors Hydrogen peroxide Medicine (General) R5-920 Biology (General) QH301-705.5
spellingShingle	Ischemic stroke Ischemia/reperfusion Hypoxia/reoxygenation In vivo optical brain interrogation Genetically encoded fluorescent biosensors Hydrogen peroxide Medicine (General) R5-920 Biology (General) QH301-705.5 Ilya V. Kelmanson Arina G. Shokhina Daria A. Kotova Matvei S. Pochechuev Alexandra D. Ivanova Alexander I. Kostyuk Anastasiya S. Panova Anastasia A. Borodinova Maxim A. Solotenkov Evgeny A. Stepanov Roman I. Raevskii Aleksandr A. Moshchenko Valeriy V. Pak Yulia G. Ermakova Gijsbert J.C. van Belle Viktor Tarabykin Pavel M. Balaban Ilya V. Fedotov Andrei B. Fedotov Marcus Conrad Ivan Bogeski Dörthe M. Katschinski Thorsten R. Doeppner Mathias Bähr Aleksei M. Zheltikov Dmitry S. Bilan Vsevolod V. Belousov In vivo dynamics of acidosis and oxidative stress in the acute phase of an ischemic stroke in a rodent model
description	Ischemic cerebral stroke is one of the leading causes of death and disability in humans. However, molecular processes underlying the development of this pathology remain poorly understood. There are major gaps in our understanding of metabolic changes that occur in the brain tissue during the early stages of ischemia and reperfusion. In particular, it is generally accepted that both ischemia (I) and reperfusion (R) generate reactive oxygen species (ROS) that cause oxidative stress which is one of the main drivers of the pathology, although ROS generation during I/R was never demonstrated in vivo due to the lack of suitable methods. In the present study, we record for the first time the dynamics of intracellular pH and H2O2 during I/R in cultured neurons and during experimental stroke in rats using the latest generation of genetically encoded biosensors SypHer3s and HyPer7. We detect a buildup of powerful acidosis in the brain tissue that overlaps with the ischemic core from the first seconds of pathogenesis. At the same time, no significant H2O2 generation was found in the acute phase of ischemia/reperfusion. HyPer7 oxidation in the brain was detected only 24 h later. Comparison of in vivo experiments with studies on cultured neurons under I/R demonstrates that the dynamics of metabolic processes in these models significantly differ, suggesting that a cell culture is a poor predictor of metabolic events in vivo.
format	article
author	Ilya V. Kelmanson Arina G. Shokhina Daria A. Kotova Matvei S. Pochechuev Alexandra D. Ivanova Alexander I. Kostyuk Anastasiya S. Panova Anastasia A. Borodinova Maxim A. Solotenkov Evgeny A. Stepanov Roman I. Raevskii Aleksandr A. Moshchenko Valeriy V. Pak Yulia G. Ermakova Gijsbert J.C. van Belle Viktor Tarabykin Pavel M. Balaban Ilya V. Fedotov Andrei B. Fedotov Marcus Conrad Ivan Bogeski Dörthe M. Katschinski Thorsten R. Doeppner Mathias Bähr Aleksei M. Zheltikov Dmitry S. Bilan Vsevolod V. Belousov
author_facet	Ilya V. Kelmanson Arina G. Shokhina Daria A. Kotova Matvei S. Pochechuev Alexandra D. Ivanova Alexander I. Kostyuk Anastasiya S. Panova Anastasia A. Borodinova Maxim A. Solotenkov Evgeny A. Stepanov Roman I. Raevskii Aleksandr A. Moshchenko Valeriy V. Pak Yulia G. Ermakova Gijsbert J.C. van Belle Viktor Tarabykin Pavel M. Balaban Ilya V. Fedotov Andrei B. Fedotov Marcus Conrad Ivan Bogeski Dörthe M. Katschinski Thorsten R. Doeppner Mathias Bähr Aleksei M. Zheltikov Dmitry S. Bilan Vsevolod V. Belousov
author_sort	Ilya V. Kelmanson
title	In vivo dynamics of acidosis and oxidative stress in the acute phase of an ischemic stroke in a rodent model
title_short	In vivo dynamics of acidosis and oxidative stress in the acute phase of an ischemic stroke in a rodent model
title_full	In vivo dynamics of acidosis and oxidative stress in the acute phase of an ischemic stroke in a rodent model
title_fullStr	In vivo dynamics of acidosis and oxidative stress in the acute phase of an ischemic stroke in a rodent model
title_full_unstemmed	In vivo dynamics of acidosis and oxidative stress in the acute phase of an ischemic stroke in a rodent model
title_sort	in vivo dynamics of acidosis and oxidative stress in the acute phase of an ischemic stroke in a rodent model
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/1a45f757a0164abd98bbabfc20e1314f
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In vivo dynamics of acidosis and oxidative stress in the acute phase of an ischemic stroke in a rodent model

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